i+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, nave 15, 01510 Vitoria-Gasteiz, Spain; Grupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spain.
i+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, nave 15, 01510 Vitoria-Gasteiz, Spain.
Mater Sci Eng C Mater Biol Appl. 2021 Jun;125:112102. doi: 10.1016/j.msec.2021.112102. Epub 2021 Apr 16.
Hyaluronic acid (HA) solutions were crosslinked with divinyl sulfone (DVS) and subsequently loaded with antibiotic molecules to obtain biocompatible and antibacterial injectable hydrogels. The crosslinking degree of the hydrogels was modulated by varying the reaction time and the HA:DVS weight ratio. Synthesized HA-DVS hydrogels were characterized by their rheological properties, pore size, swelling capacity and hydrolytic and thermal degradation. Biocompatibility was assessed by measuring pH, osmolality and by in vitro cytotoxic assay. Acetyl salicylic (AAS) loaded hydrogels display anti-inflammatory properties in vitro, whereas cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) loaded hydrogels show in vitro antibacterial activity against Staphylococcus aureus. The combine use of antibiotics and AAS produces a synergic effect that reduces the S. aureus population up to a log10 reduction (R) of 5.55. Overall results show that antibiotic/AAS loaded HA-DVS hydrogels could be effectively used to combat S. aureus infections and to increase the antibacterial activity of antibiotics commonly used against S. aureus.
透明质酸（HA）溶液与二乙烯砜（DVS）交联，然后负载抗生素分子，以获得具有生物相容性和抗菌性的可注射水凝胶。水凝胶的交联程度通过改变反应时间和 HA:DVS 重量比来调节。合成的 HA-DVS 水凝胶通过流变特性、孔径、溶胀能力以及水解和热降解进行表征。通过测量 pH 值、渗透压和体外细胞毒性试验来评估生物相容性。载有乙酰水杨酸（AAS）的水凝胶在体外显示出抗炎特性，而载有头孢呋辛（CFX）、四环素（TCN）和阿莫西林（AMX）的水凝胶对金黄色葡萄球菌具有体外抗菌活性。抗生素和 AAS 的联合使用产生协同作用，使金黄色葡萄球菌的数量减少了 5.55 个对数减少值（R）。总体结果表明，载有抗生素/AAS 的 HA-DVS 水凝胶可有效用于对抗金黄色葡萄球菌感染，并提高金黄色葡萄球菌常用抗生素的抗菌活性。
